RAD51 and XRCC3 polymorphisms: impact on the risk and treatment outcomes of de novo inv(16) or t(16;16)/CBFβ-MYH11(+) acute myeloid leukemia.

Abstract

DNA double-strand break repair via homologous recombination (HR) is essential in maintaining genetic integrity, and may modulate susceptibility to the development of acute myeloid leukemia (AML) and influence outcomes of AML. This study was designed to evaluate the effects of polymorphisms in HR repair genes RAD51 and XRCC3 on the risk and treatment outcomes of inv(16)/t(16;16)/CBFβ-MYH11(+) AML. The distribution of polymorphisms in RAD51-G135C and XRCC3-Thr241Met were studied by PCR-RFLP analysis in 625 cases of de novo AML, including 105 cases with inv(16)/t(16;16)/CBFβ-MYH11, 806 family controls and 704 volunteer controls. It was found that the XRCC3-241Met variant significantly increased the risk of the development of the AML with inv(16)/t(16;16) as compared with both the volunteer control (OR=7.22; 95% CI, 4.37-11.91) and the family control (OR=7.99; 95% CI, 5.03-12.69). A retrospective study conducted in 103 inv(16)/t(16;16) AML patients. In multivariate analysis for the potential prognostic factors, the XRCC3-241Met variant significantly reduced disease-free survival (DFS) in complete remission (CR) achieved patients (HR=2.34, 95% CI, 1.32-4.16). These data indicate that the XRCC3-241Met variant may not be only a susceptibility factor to the AML with inv(16)/t(16;16), but also an independent poor-prognostic factor for this AML subtype.

• Authors: Liang Liu, Lin Yang, Yingchang Mi, Jianxiang Wang, Jianyong Li, Yue Zhang, Xiaotang Ma, Tiejun Qin, Zefeng Xu, Zhijian Xiao
• Journal: Leukemia research (Leuk Res) Vol. 35 Issue 8 Pg. 1020-6 (Aug 2011) ISSN: 1873-5835 [Electronic] England
• PMID: 21296419 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• CBFbeta-MYH11 fusion protein
• DNA, Neoplasm
• DNA-Binding Proteins
• Oncogene Proteins, Fusion
• X-ray repair cross complementing protein 3
• RAD51 protein, human
• Rad51 Recombinase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Case-Control Studies
• Child
• Child, Preschool
• Chromosome Inversion
• Chromosomes, Human, Pair 16 (genetics)
• DNA, Neoplasm (genetics)
• DNA-Binding Proteins (genetics)
• Female
• Follow-Up Studies
• Genotype
• Humans
• Leukemia, Myeloid, Acute (genetics, therapy)
• Male
• Middle Aged
• Oncogene Proteins, Fusion (genetics)
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Polymorphism, Restriction Fragment Length
• Rad51 Recombinase (genetics)
• Retrospective Studies
• Survival Rate
• Translocation, Genetic
• Treatment Outcome
• Young Adult